Four children with familial hyperlysinemia have been studied in this laboratory. From results thus obtained and data reported elsewhere, it can be shown that a deficiency of lysine:ketoglutarate reductase activity in these patients prevents them from converting lysine to saccharopine. Similarly, an alternate path of lysine catabolism by way of pipecolic acid has been demonstrated for them. Further studies propose to: (1) Using liver from a hyperlysinemic, study the capacity of such tissue to convert L-lysine to pipecolic acid and compare results with similar studies performed on normal human liver. (2) Using the assay system developed for the above, determine the capacity of liver from neonates and from young infants to convert lysine to saccharopine and to pipecolic acid, in order to learn why 2 hyperlysinemics failed to display hyperlysinemia until they were 6 months old. (3) Determine levels of pipecolic acid and piperidine in normal and hyperlysinemic brain. (4) Attempt to assay the capacity of hyperlysinemic brain to convert pipecolic acid to piperidine. (5) Determine hypusine levels in liver, kidney, muscle and brain from hyperlysinemic and normal individuals. (6) Continue long-term clinical & biochemical monitoring of 3 living children with familial hyperlysinemia.